Adolescents with clinical type 1 diabetes display reduced red blood cell glucose transporter isoform 1 (GLUT1)

Type 1 diabetic (T1D) adolescent children on insulin therapy suffer episodes of both hyper‐ and hypoglycemic episodes. Glucose transporter isoform GLUT1 expressed in blood–brain barrier (BBB) and red blood cells (RBC) compensates for perturbed circulating glucose toward protecting the supply to brain and RBCs. We hypothesized that RBC‐GLUT1 concentration, as a surrogate for BBB‐GLUT1, is altered in T1D children. To test this hypothesis, we measured RBC‐GLUT1 by enzyme‐linked immunosorbent assay (ELISA) in T1D children (n = 72; mean age 15.3 ± 0.2 yr) and control children (CON; n = 11; mean age 15.6 ± 0.9 yr) after 12 h of euglycemia and during a hyperinsulinemic–hypoglycemic clamp with a nadir blood glucose of ?3.3 mmol/L for 90 min (clamp I) or ?3 mmol/L for 45 min (clamp II). Reduced baseline RBC‐GLUT1 was observed in T1D (2.4 ± 0.17 ng/ng membrane protein); vs. CON (4.2 ± 0.61 ng/ng protein) (p < 0.0001). Additionally, baseline RBC‐GLUT1 in T1D negatively correlated with hemoglobin A1c (HbA1c) (R = ?0.23, p < 0.05) but not in CON (R = 0.06, p < 0.9). Acute decline in serum glucose to 3.3 mmol/L (90 min) or 3 mmol/L (45 min) did not change baseline RBC‐GLUT1 in T1D or CON children. We conclude that reduced RBC‐GLUT1 encountered in T1D, with no ability to compensate by increasing during acute hypoglycemia over the durations examined, may demonstrate a vulnerability of impaired RBC glucose transport (serving as a surrogate for BBB), especially in those with the worst control. We speculate that this may contribute to the perturbed cognition seen in T1D adolescents.